Toxicity of a serotonin-derived neuromelanin

Miller, Elizabeth; Fibuch, Eugene E.; Seidler, Norbert W.

doi:10.1016/j.bbrc.2009.12.085

Cited by 5 publications

(15 citation statements)

References 22 publications

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“…Pre-treatment versus control: P = 0.66; co-treatment versus control: P \ 0.05 catecholamine-derived neuromelanin [20]. We previously showed that low concentrations of SDM (less than 2 lg/mL) cause membrane disorganization of unilamellar vesicles [15] consistent with the current study and suggesting that the mechanism of cell toxicity may in part be due to intercalation of SDM into the cell's lipid bilayer. We previously proposed that SDM is a neuromelaninlike compound [7], which exhibits many of the same physio-chemical properties that are seen with eumelanin, the major form of neuromelanin.…”

Section: Discussionsupporting

confidence: 89%

“…Interestingly, sevoflurane, a commonly used inhaled anesthetic, sequesters acrolein [7] and enhances the formation of a serotoninderived melanoid (SDM), which may act to deplete serotonin and thus contribute to POCD. We further showed that SDM exhibits redox properties [14] and disrupts lipid bilayers [15]. We know from these studies that SDM is reddish brown in color and quite large with a limit structure of approximately 50-70 kDa.…”

Section: Introductionmentioning

confidence: 77%

“…Interestingly, neuromelanin analysis shows aliphatic components [23] that may enable these structures to penetrate lipid bilayers of cells. Acrolein, which polymerizes to form polyacrolein [24], may generate aliphatic extensions to SDM that allow it to disrupt acyl chains and phospholipid head groups as seen with studies using unilamellar vesicles [15].…”

Section: Discussionmentioning

confidence: 99%

“…While serotonin's reactive nature with various agents (i.e. acrolein, copper ions) may result in localized depletion thus promoting cognitive impairment, serotonin metabolites like bitryptamine [11] or SDM [7,14,15] appear to be have noxious properties, suggesting a cytotoxic mechanism for POCD.…”

Section: Introductionmentioning

confidence: 99%

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Carnosine Protects Against the Neurotoxic Effects of a Serotonin-Derived Melanoid

et al. 2010

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Anesthesia-related postoperative cognitive dysfunction (POCD) leads to morbidity in the elderly. Lipid peroxidative byproducts (i.e. acrolein) accumulate in aging and may play a role. Sevoflurane, an inhaled anesthetic, sequesters acrolein and enhances the formation of a serotonin-derived melanoid (SDM). SDM may be a biologically relevant polymeric melanoid that we previously showed exhibits redox activity and disrupts lipid bilayers. In this study, we examined the toxicity of SDM in cell culture and looked at protection using L-carnosine. SDM's toxic effects were tested on neuronal-like SH-SY5Y cells, causing an exponential decrease in viability, while human dermal fibroblasts were completely resistant to the toxic effects. SDM brought about morphological changes to differentiated SH-SY5Y cells, particularly to neuronal processes. Co- but not pre-treatment with L-carnosine protected differentiated SH-SY5Y cells exposed to SDM. Our mechanism suggests focal sevoflurane-induced sequestration of age-related acrolein leading to SDM synthesis and neuronal impairment, which is prevented by L-carnosine.

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Section: Discussionsupporting

confidence: 89%

Section: Introductionmentioning

confidence: 77%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Carnosine Protects Against the Neurotoxic Effects of a Serotonin-Derived Melanoid

et al. 2010

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“…The mechanisms that contribute to POCD are poorly understood, particularly at the molecular level. We propose that POCD may be associated with the toxic products of lipid peroxidation (Roberts et al 2007;Miller et al 2010). Acrolein, a bifunctional a,b-unsaturated aldehyde, accumulates in aging (Poon et al 2004;Williams et al 2006), creating an environment in the elderly brain that increases its susceptibility to neurotoxic processes.…”

Section: Introductionmentioning

confidence: 99%

Redox Mechanism of Neurotoxicity by a Serotonin–Acrolein Polymeric Melanoid

et al. 2010

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Postoperative cognitive dysfunction may be associated with the toxic products of lipid peroxidation, such as the α,β-unsaturated aldehyde acrolein, which accumulates in aging. We previously identified an acrolein-mediated, serotonin-derived melanoid product, or SDM. This study further characterizes this putative novel neuromelanin, which is not made from catecholamines. In addition to its strong protein-binding properties, we observed that SDM binds Fe(2+) readily and exhibits complex redox characteristics. SDM may exist as a two-dimensional network of polymers that coalesce into larger entities exhibiting electroactive properties. These observations suggest that SDM may contribute to the decline in cognition due to focal degeneration from SDM-mediated free-radical production. We know that inhalational anesthetics sequester acrolein, which is toxic to neurons, and we propose that the local increase in acrolein depletes serotonin levels and enhances neuronal vulnerability through the production of neuromelanin-like structures, such as SDM.

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Polysaccharide-mediated synthesis of melanins from serotonin and other 5-hydroxy indoles

Vercruysse

Clark

Alatas

et al. 2017

Preprint

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As a continuation of our research on the melanin formation from catecholamines, we studied the polysaccharidemediated oxidation of serotonin and other 5-hydroxy indoles into melanin-like materials. As for the catecholamines, we observed that many polysaccharides promote the oxidation of such compounds, particularly in the presence of Cu 2+. The reactions were monitored using RP-HPLC and SEC techniques. Melanin-like materials were purified through dialysis and evaluated using UV_Vis and FT_IR spectroscopic techniques. One such material, synthesized from chondroitin sulfate type A and serotonin in the presence of Cu 2+ was found to affect the release of IL-1 and IL-6 cytokines from immune cells.

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Toxicity of a serotonin-derived neuromelanin

Cited by 5 publications

References 22 publications

Carnosine Protects Against the Neurotoxic Effects of a Serotonin-Derived Melanoid

Carnosine Protects Against the Neurotoxic Effects of a Serotonin-Derived Melanoid

Redox Mechanism of Neurotoxicity by a Serotonin–Acrolein Polymeric Melanoid

Polysaccharide-mediated synthesis of melanins from serotonin and other 5-hydroxy indoles

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